Cisplatin (cis-diamminedichloridoplatinum(II)) is a mononuclear platinum(II) complex in which two chloride ions and 2 ammines are coordinated in the cis configuration and is widely used in chemotherapy as one of the most effective anticancer agents. In addition, cisplatin analogues such as carboplatin, nedaplatin, and oxaliplatin are in clinical use in order to counter cancer cell resistance and the side effects of cisplatin therapy.
The formation by cisplatin of a 1,2-intrastrand crosslink with the DNA strand within the cell and the resulting generation of substantial distortion in the DNA strand are believed to participate in the mode of action of this complex and its metabolic pathway in vivo (Non-patent Reference 1). The platinum drugs cited above that are structural analogues to cisplatin are also believed to bind to DNA by the same mode.
On the other hand, the development is desired of platinum drugs that have a drug profile different from that of these existing platinum drugs. One approach considered to be effective for this is the design of platinum complex compounds that differ from the existing cisplatin-type drugs with regard to mode of action and/or in vivo metabolic pathway. For example, the generation of a drug profile different from that of the cisplatin-type platinum drugs can be expected for a platinum complex (for example, a multinuclear platinum complex) that, as a consequence of having a molecular structure substantially different from that of cisplatin, can bind to DNA through a mode different from that for cisplatin. Patent Reference 1 and Non-patent References 2 and 3 are examples of prior art references involved with this type of technology.    Patent Reference 1: WO 96/16068    Non-patent Reference 1: Jamieson, E. R. and Lipperd, S. J. “Structure, Recognition, and Processing of Cisplatin-DNA Adducts” Chem. Rev., 1999, 99, 2467-2498.    Non-patent Reference 2: Kasparkova, J.; Zehnulova, J.; Farrell, N.; and Brabec, V. “DNA interstrand cross-links of the novel antitumor trinuclear platinum complex BBR3464. Conformation, recognition by high mobility group domain proteins, and nucleotide excision repair.” J. Biol. Chem., 2002, 277, (50), 48076-48086.    Non-patent Reference 3: Komeda, S.; Lutz, M.; Spek, A. L.; Chikuma, M.; and Reedijk, J. “New antitumor-active azole-bridged dinuclear platinum(II) complexes: synthesis, characterization, crystal structures, and cytotoxic studies.” Inorg. Chem., 2000, 39, (19), 4230-4236.